Copper() complexes with tridentate Schiff base-like ligands: solid state and solution structures and anticancer activity

• Published in: Dalton transactions : an international journal of inorganic chemistry 2019-10, Vol.48 (4), p.1522-1523
• Main Authors: Dankhoff, Katja, Gold, Madeleine, Kober, Luisa, Schmitt, Florian, Pfeifer, Lena, Dürrmann, Andreas, Kostrhunova, Hana, Rothemund, Matthias, Brabec, Viktor, Schobert, Rainer, Weber, Birgit
• Format: Article
• Language: English
• Subjects: Anticancer properties; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Survival - drug effects; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Coordination compounds; Copper; Copper - chemistry; Copper - pharmacology; Copper compounds; Crystal structure; Crystallography; DNA Topoisomerases, Type I - metabolism; Humans; Imines; Ligands; Molecular Structure; Pyridines - chemistry; Pyridines - pharmacology; Schiff Bases - chemistry; Single crystals; Solutions; Structure-Activity Relationship
• ISSN: 1477-9226; 1477-9234
• DOI: 10.1039/c9dt02571e

We report 15 new Cu( ii ) complexes with tridentate NNO β-acylenamino ligands derived from 2-picolylamine and bearing up to three alkyl, alkoxy, alkoxycarbonyl, or (pseudo)halide substituents. The structures of nine complexes were elucidated by single crystal X-ray diffraction analysis. Complexes with an unsubstituted pyridine ring crystallised with a square pyramidal coordination sphere, whereas substitution of the pyridine ring led to a square planar coordination sphere around the metal centre. The solution structures and properties of the complexes were characterised by UV-Vis spectroscopy and cyclic voltammetry. They were also tested for their cytotoxic effect on four human cancer cell lines. Two complexes were identified that were highly active with single-digit IC 50 values, exceeding those of cisplatin by far. A tentative structure-activity relationship was proposed as well as topoisomerase I inhibition as a possible mode of action, while any significant interference with DNA and the level of reactive oxygen species could be excluded. We report 15 new Cu( ii ) complexes with tridentate NNO β-acylenamino ligands derived from 2-picolylamine and bearing up to three alkyl, alkoxy, alkoxycarbonyl, or (pseudo)halide substituents.